Benfotiamine
Background
Benfotiamine (S-benzoylthiamine-O-monophosphate) is a naturally-occurring fat-soluble form of thiamine (vitamin B-1). However, benfotiamine is believed to be more available to the body than its water soluble counterparts, about five times as great as from conventional thiamine supplements. Benfotiamine is the most potent of the allithiamines, a unique class of thiamine related compounds present in trace quantities in roasted crushed garlic and other members of the Allium genus (such as onions, shallots, and leeks). I
It has been known for some time that thiamine (vitamin B-1) plays an essential role in the metabolism of glucose, through the actions of its co-enzyme TPP (thiamine pyrophosphate). In the cell, glucose is metabolized in the presence of TPP, and thus TPP is vital to the cell’s energy supply and metabolism of glucose. Benfotiamine, acting as a ‘super-charged’ thiamine, helps maintain healthy cells in the presence of excess blood glucose. It does this through several different mechanisms.
Mechanism of Action
If glucose is maintained at normal levels, excess glucose metabolites do not accumulate within the cell. In the presence of elevated glucose levels, however, the electron transport chain, the final ATP-generating system in the mitochondrion, produces larger than normal amounts of oxygen free-radical superoxide. This excess superoxide inhibits the conversion of glucose to pyruvic acid, resulting in an excess of intermediate metabolites, which trigger several mechanisms that result in potential damage to vascular tissue. Cells particularly vulnerable to this type of damage are found in the retina, kidneys, and nerves.
Benfotiamine has been shown to block three of these mechanisms: the hexosamine pathway, the diaglycerol-protein kinease C pathway, and the formation of advanced glycation end-products (AGEs). Benfotiamine does this by stimulating tranketolase, a cellular enzyme essential for maintenance of normal glucose metabolic pathways. Studies done in diabetic rats have shown that benfotiamine counteracts these metabolic abnormalities caused by elevated blood glucose.
Clinical Studies
Advanced Glycation End Product (AGE)
AGE is formed through abnormal linkages between proteins and glucose. This can cause damage to proteins, such as collagen, the major structural protein in connective tissue. This occurs via a reaction similar to the ‘browning reaction’ that takes place in the cooking and storage of food. High glucose concentrations encourage this, while normal blood glucose levels return decrease it.
Because collagen in the body is meant to last, it is more susceptible than other proteins to damage. And because collagen supports a healthy blood vessel wall, damage to collagen compromises vascular function. Furthermore, a number of other potentially harmful events may also occur, including immune mediated inflammation that further increases vascular permeability. Accordingly, it is vitally important to support normal glucose metabolic pathways so that formation of AGE is minimized.
Benfotiamine, in the test tube, has been shown to prevent AGE formation in endothelial cells (cells that make up the membranes that line the inner walls of organs and blood vessels) cultured in high glucose. In another study examining the effects of benfotiamine versus water-soluble thiamin, benfotiamine inhibited AGE formation while AGE levels were not significantly altered by thiamin. Of even greater interest, benfotiamine normalized nerve function in the animals. After 6 months of administration, nerve function was normalized by benfotiamine, but not thiamine. In another animal study, benfotiamine was administered to rats with elevated glucose levels, resulting in kidney damage. Benfotiamine improved kidney function and prevented protein leakage into the urine, a commonly used measure of kidney health.
Diabetic Neuropathy
In one trial, 24 people suffering with diabetic neuropathy took either benfotiamine (plus doses of common vitamin B-6 and B-12 similar to those used in mutivitamins) or a placebo, for 12 weeks. The benfotiamine treatment group started with 320 mg of benfotiamine per day for the first 2 weeks, followed by 120 mg for the rest of the trial. Before and after the trial, the function of patients’ nerve cells were tested using nerve conduction velocity (NCV) and vibratory perception threshold (when vibrations applied at key nerve sites are first felt). At the end of the trial, the vibration perception threshold had improved by 30% in those who had taken the benfotiamine supplements, while it had worsened in the placebo group. People taking Benfotiamine also experienced a statistically significant improvement in nerve conduction velocity from the feet, while this aspect of nerve function deteriorated in those taking the placebo. No adverse events were reported.
The therapeutic effectiveness of a benfotiamine in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP) was studied in a 6-week open clinical trial. Thirty-six patients were randomly assigned to three groups, each of them comprising 12 participants. One group was given low-dose benfotiamine, while the other groups were given either high-dose benfotiamine plus a standard B vitamin combination or medium-dose benfotiamine plus a standard B vitamin combination. Neuropathy was assessed by five parameters, including the sensation of pain, the vibration sensation, and the current perception threshold.
An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study, and a significant improvement in most of the parameters studied appeared already at the third week of therapy. The greatest change occurred in the group of patients receiving the high dose. The authors concluded that “benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.” Furthermore, benfotiamine users have reported 50% to 88% reduction in diabetic nerve pain, depending on the dosage used and the study length, as well as increased ability of the nerves to detect an electrical current.
Retinal Damage
Studies have also begun to document the ability of benfotiamine to protect the tissues of the eye from AGE damage. One study tested the ability of a thiamin/benfotiamine combination to protect the retinas of diabetic rats. The researchers then gave one group of rodents benfotiamine supplements, and left another group unsupplemented. Nine months later, the level of AGE in the retinas of the animals receiving benfotiamine was normal and did not exhibit diabetic retinal damage. Overall, the number of damaged capillaries in the supplemented diabetic animals was indistinguishable from that of their non-diabetic healthy counterparts.
Kidney Damage
Diabetic nephropathy (kidney damage) is a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. In an animal study, therapy with a thiamine/benfotiamine combination countered the accumulation and inhibited the development of nephropathy and strongly inhibited the development of microalbuminuria (protein in the urine due to kidney damage). The authors concluded that “benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.” Further studies are underway to see if benfotiamine can improve kidney function in diabetic animals with pre-existing kidney damage, as it has already been shown to do in the nerves of diabetic animals and humans.
Dosage
Benfotiamine therapy should only be undertaken with the guidance of a healthcare practitioner familiar with its use.
